Junk. Barren. Non-functioning. Dark matter. That’s how scientists had described the 98% of human genome that lies between our 21,000 genes, ever since our DNA was first sequenced about a decade ago. The disappointment in those descriptors was intentional and palpable.

It had been believed that the human genome — the underpinnings of the blueprint for the talking, empire-building, socially evolved species that we are — would be stuffed with sophisticated genes, coding for critical proteins of unparalleled complexity. But when all was said and done, and the Human Genome Project finally determined the entire sequence of our DNA in 2001, researchers found that the 3 billion base pairs that comprised our mere 21,000 genes made up a paltry 2% of the entire genome. The rest, geneticists acknowledged with unconcealed embarrassment, was an apparent biological wasteland.

But it turns out they were wrong. In an impressive series of more than 30 papers published in several journals, including Nature, Genome Research, Genome Biology, Science and Cell, scientists now report that these vast stretches of seeming “junk” DNA are actually the seat of crucial gene-controlling activity — changes that contribute to hundreds of common diseases. The new data come from the Encyclopedia of DNA Elements project, or ENCODE, a $123 million endeavor begun by the National Human Genome Research Institute (NHGRI) in 2003, which includes 442 scientists in 32 labs around the world.

ENCODE has revealed that some 80% of the human genome is biochemically active. “What is remarkable is how much of [the genome] is doing at least something. It has changed my perception of the genome,” says Ewan Birney, ENCODE’s lead analysis coordinator from the European Bioinformatics Institute.

Rather than being inert, the portions of DNA that do not code for genes contain about 4 million so-called gene switches, transcription factors that control when our genes turn on and off and how much protein they make, not only affecting all the cells and organs in our body, but doing so at different points in our lifetime. Somewhere amidst that 80% of DNA, for example, lie the instructions that coax an uncommitted cell in a growing embryo to form a brain neuron, or direct a cell in the pancreas to churn out insulin after a meal, or guide a skin cell to bud off and replace a predecessor that has sloughed off.

“What we learned from ENCODE is how complicated the human genome is, and the incredible choreography that is going on with the immense number of switches that are choreographing how genes are used,” Eric Green, director of NHGRI, told reporters during a teleconference discussing the findings. “We are starting to answer fundamental questions like what are the working parts of the human genome, the parts list of the human genome and what those parts do.”

If the Human Genome Project established the letters of the human genome, ENCODE is providing the narrative of the genetic novel by fashioning strings of DNA into meaningful molecular words that together tell the story not just of how we become who we are, but how we get sick as well.

Ever since the human genome was mapped, scientists have been mining it for clues to the genetic triggers and ultimately the treatments for a variety of diseases — heart disease, diabetes, schizophrenia, autism, to name just a few. But hundreds of so-called genome-wide association studies (GWAS) that have compared the DNA of healthy individuals to those with specific diseases revealed that the relevant changes in DNA were occurring not in the genes themselves, but in the non-coding genetic black holes. Until now, researchers didn’t fully understand what these non-coding regions did; if variations in these areas were not part of a known gene, they couldn’t tell what impact, if any, the genetic change had.

ENCODE, which provides a map of those genetic switches, will now allow scientists to determine what exactly those variants do; it’s likely that their function in regulating and controlling key genes can now be traced and studied — and hopefully manipulated to treat whatever disease they contribute to. “We need to revisit the interpretation of those studies,” Dr. John Stamatoyannopoulos, associate professor medicine and genome sciences at University of Washington, said during the teleconference. “In many cases those studies concluded that 10 or 15 variants might be important for a particular disease. ENCODE data points to the fact that this is probably a significant underestimate, that there may be dozens, even hundreds of variants landing in switches so there is a tremendous amount of information still hidden within those studies that needs to be reanalyzed in the context of the new data.”

Eager to put their new found scientific knowledge to work, scientists have already begun some of those studies. At Washington University, Stamatoyannopoulos and his colleagues found that gene changes identified by GWAS as involved in 17 different types of cancer seem to affect nearly two dozen transcription factors that translate raw DNA into the RNA that turns into functional proteins. This common molecular thread may lead to new treatments that control the function of these transcription factors in not just one but all 17 cancers, including ovarian, colon and breast diseases. “This indicates that many cancers may have a shared underlying genetic predisposition,” he told reporters. “So we can make connections between diseases and genome control circuitry to understand relationships where previously there was no evidence of any connection between the diseases.”

ENCODE may shed significant light on our most common chronic diseases, including diabetes, heart disease and hypertension, which result from a complex recipe of dysfunction, not just in single genes like, but in a variety of hormones, enzymes and other metabolic factors. Changes in the way some genes are turned on or off may explain the bulk of these conditions, and ultimately make them more treatable. “By and large, we believe rare diseases may be caused by mutations in the protein [or gene-]coding region,” says Green, while the “more common, complicated diseases may be traced to genetic changes in the switches.”

In another example of ENCODE’s power, Birney says the genetic encyclopedia has also identified a new family of regulators that affect Crohn’s disease, an autoimmune disorder that causes the body’s immune cells to turn on intestinal cells. The finding could lead to novel, potentially more effective therapies. “I’ve had more clinical researchers come to my door in the past two years than in the previous 10,” Birney said. “It’s going to be really good fun producing lots of insights into disease over the next couple of years.”

Not only does ENCODE open doors to new therapies, it also furthers our basic understanding of human development. At the heart of many genetic researchers’ investigations is the desire to understand how each cell in our body, from those that make up our hair to those that reside in our toenails, can contain our entire genome yet still manage to look and function in such widely divergent ways. ENCODE’s scientists knew that certain regulatory mechanisms dictated when and where certain genes were expressed and in what amount in order to give rise to the diversity of cells and tissues that make up the human body, but even they were surprised by just how intricate the choreography turned out to be. “Most people are surprised that there is more DNA encoding regulatory control elements, or switch elements for genes, than for the genes themselves,” Michael Snyder, director of the center for genomics and personalized medicine at Stanford University and a member of the ENCODE team, told Healthland.

In keeping with the open-access model established by the Human Genome Project, ENCODE’s data is available in its entirety to researchers for free on the consortium’s website. The database will undoubtedly fuel a renewed interest in genome-based approaches to both diagnosing and treating disease. Despite initial excitement in the field, in the years since the genome was mapped, gene-guided treatments and gene-therapy approaches to treating disease have proven difficult to bring to the clinic; part of the challenge, geneticists now say, may have been related to the fact that they didn’t fully understand how to control the genes that were affected by disease.

“I am pretty sure this is the science for this century,” Birney said. “We are going to work out how we make humans, starting from the simple instruction manual.” And perhaps we’ll figure out how to make humans healthier as well.

As a sci fi writer with a geneticist for a main character, I've been keeping track of genes for a very long time.

The
very first time I heard "junk DNA" referred to that way, especially in
the context I heard it, I knew it was likely not actually not "junk",
just not something that marked stuff we'd already discovered.

The article says that "junk DNA" is how scientists had described the 98% of the human genome that lies between our 21,000 genes. You left out a very important qualifier. SOME scientists said it, most of us knew better from day one. I was a graduate student when the first use of the term "junk DNA" occurred in this context, and it was never accepted by those of us who had a clue. I and many of my fellow students silently laughed at the combination of arrogance and ignorance that this moniker represented. The concept is as unscientific as it can be, and to me is akin to invoking the supernatural because YOU don't know how something works and it must therefore be unexplainable by science. That's the same argument that creationists like Michael Behe use, and it is, to put it simply, BS.

As a sci fi writer with a geneticist for a main character, I've been keeping track of genes for a very long time.

The very first time I heard "junk DNA" referred to that way, especially in the context I heard it, I knew it was likely not actually not "junk", just not something that marked stuff we'd already discovered.

"At the heart of many genetic researchers’ investigations is the desire to understand how each cell in our body, from those that make up our hair to those that reside in our toenails, can contain our entire genome yet still manage to look and function in such widely divergent ways. "

I'm surprised that they were surprised - as if the stuff they didn't know and understand was meaningless. Duh. And it's not even the genome that makes cells function but also how cells communicate and act together in proximity (extracellular matrix).

I analyzed my junk DNA. It's actually an encrypted history of the Androms, an ancient civilization in the Andromeda Galaxy that vanished long ago.

It seems that, while visiting the Milky Way, they inserted it into the DNA of the first eurkaryotes on a myriad rocky planets, awaiting decryption by the sentient civilizations that would eventually evolve there.

But the science was settled! The experts were agreed for decades that 90% of our DNA was junk; and that evolution, or Gaia, or The Red Headed League had "made a mistake" with our genetic code. Gee, looks like it's not so after all. But it's cute how when scientismists can't see the reason for something they conclude there isn't one; not that they simply don't know enough to enable them to see it.

The more intricate the 'choreography' the more chance there is of screwing it up. I applaud the research but my concern is that tinkering is the next step and that way lies the path of unintended consequences.

It was the religion of atheism and evolution that labeled it "junk DNA" ... "the garbage left over from the evolutionary process", they said. Yet when you tamper with it, what happens? Things like cancer and death. So clearly it does have present tense purpose. But for years the standing position of the scientific community was that anyone who disagreed with the idea that it's "junk DNA" was a fundamentalist of one sort or another because scientists don't make mistakes and there is no politics in science. Yeah, right.

I've heard that a good modern analogy for how the genetic code operates in cells is to think in terms of circuits and networks. I'm starting to think that maybe the genetic code is also like an overinflated bureaucracy or corporation with more management than workers. The switches are the managers and bureaucrats and the genes are the ones who are more directly involved in protein formation.

When I saw the title, I though this was a decade-old article that had suddenly trended on Time.com. When Birney says "Science of the century" perhaps he meant 20th century; when I started my undergrad in 1998 the fact that "junk DNA" offered much more than meets the eye was already known...

This is unbelievalbe. This degenerate perverted term had nothing to do with the Press or any other media and the Ideolgues here know that.

The scientist who is credited with coining the term “‘junk’ DNA” was evolutionist Susumu Ohno. In his paper “So Much ‘Junk’ DNA in Our Genome,” he wrote that the remaining sequences of DNA “are the remains of nature’s experiments which failed. The earth is strewn with fossil remains of extinct species; is it a wonder that our genome too is filled with the remains of extinct genes?”

Later other geneticists like John S. Mattick, professor of Molecular Biology at the University of Queensland in Brisbane, Australia, refuted that irresponsible dogma by insisting we simply do not know everything and we should research to find out. The man was personally attacked and given every insult possible by people like staunch Evolutionist Larry Moran.

People here need to get over this stupid embarrassment and start doing real science and dump the ideology for the reality. Quit making excuses to the stupid blunder and move on.

Will journalists please quit saying that non-coding DNA was thought to be useless? The press are the ones that used the term "junk DNA". I don't know of any biologists who assumed that non-coding DNA was useless. (The author seems to confuse this with geneticists' surprise that our massive number of proteins is coded for by an oddly small number of genes.)

On the contrary, living things that have cell nuclei spend enormous amounts of precious energy copying this non-coding DNA, which clearly suggested that it has an adaptive benefit to the species.

This would be like finding a printed book and assuming that publishers were just blindly following tradition by adding useless margins, binding, and title page - useless because they're not readable prose. I don't know of any biologists who made this mistake.

We learned the technical terms "gene" and "DNA". Is it really so hard to learn the word "intron" or "non-coding"?

Will journalists please quit saying that non-coding DNA was thought to be useless? The press are the ones that used the term "junk DNA". I don't know any geneticists who assumed that non-coding DNA was useless. On the contrary, living things that have nuclei in their cells spend enormous amounts of precious energy copying this DNA, which clearly suggested that it has a benefit to the species.

Everything has its own function, to say that 98% of our genome is junk is unacceptable and nonsense. Time can tell the importance of this things and soon you may want to believe that indeed every single genes/genome has its unique functionality.

I believe in evolution yet not Darwinism's anti-teleological dogma. I am a Christian and am amazed at arrogance of the atheist. Atheists unfortunately, but not unexpectedly, display many of the traits of religion their caricatures and stereotypes perpetuate: intolerance and hate, close-mindedness - in addition to the inability to research history outside of their prejudices. Do not iusult good religion by associating atheism with religion.

The fact that you said atheism is a religion is laughable. And it is thought by the majority of geneticists that while all of the "junk DNA" isn't entirely useless, most of it almost certainly is functionally useless.

No, it WAS thought to be useless. I am a graduate student in Biology and I have heard my share of biologists still talk about "junk DNA" as evolutionary vestige. Some biochemistry professors online like Larry Moran STILL defend "junk DNA" as evolutionary vestige.

Journalists are reporting correctly it is just biologists unable to gulp down ego and admit our mistaken hypothesis about junk DNA. I have given paper references to the very next poster on this thread citing some papers that said junk DNA as useless and a vestige.

It is only recently that the myth of junk DNA is being junked. For the majority of 1990's early to mid 2000, junk DNA was just that.

I don't know any geneticists who assumed that non-coding DNA was useless. On the contrary, living things that have nuclei in their cells spend enormous amounts of precious energy copying this DNA, which clearly suggested that it has a benefit to the species. http://NewsUsaVote.blogspot.co...

I am a real life honest to God molecular biologist as well. "Junk DNA" is not popularization of context. It was believed to be actual evolutionary vestige that made perfect sense with logic of neo-Darwinism.

1. Popularized by paper in 1972 by Susumu Ohno. Read the paper.

2. Then Dawkins called it selfish gene was its it was "useless but harmless passenger." Read his book "The Selfish Gene"3. Francis Crick in 1980 published a paper in Nature that said Junk DNA has no function and so "it would be a folly in such cases to obsessively hunt for one."

4. Ford Dolittle in 1980 also published a paper and it reads "search for explanations may prove intellectually sterile and ultimately futile" in talking about junk DNA.

5. In 2004, some "junk DNA" in mice were deleted by Nobrega et al. and these junk "sequences may not be essential."

Throughout 1990's and also into 2000's even my molecular biology textbooks and Biochemistry textbooks have called "junk DNA" as not having any function and as an "evolutionary vestige."

When Bill Mahr was asked if he believed in "god" or religion he said: " I don't know if there is a god or not but I know one thing for certain, you don't know either". As a "christian" you are an athiest to all the other religions people believe in. So be careful about your operational definition of "arrogance" about "good religion" (which I assume is the one you believe in).

Thank you for posting these refs. Your recollection of events matches mine. The power of a theory is its predictive power and falsifiability. The idea of biological evolutionary junk has been disproved several times now. I recall how tonsils and appendix were vestigial organs left behind by evolution. I did not believe this at the time and held on to my tonsils as a young person. I'm certainly glad I did. Both tonsils and appendix are now known to have crucial immune and recovery functions. Remember the useless Glial Cells in the brain? - those globs of grey matter that didn't matter, but since they didn't seem to hurt anything they were left behind by evolution? Once again, I didn't believe it and once again the vestigial concept was proved untenable.

I first noticed a tendency for scientists to cover over what to them was embarrassing history when the steady state theory of cosmology was conclusively disproved by cosmic background radiation which made it clear that there was a start to physical reality - it had not "been here forever".What is important about your post and the comments is that they demonstrate a revisionist tendency shown by those who find their theory being falsified in plain sight over and over again. Selective memory is not conducive to real science.